Fakülteler / Faculties
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Item A Partial Epithelial-Mesenchymal Transition Signature For Highly Aggressive Colorectal Cancer Cells That Survive Under Nutrient Restriction(JOURNAL OF PATHOLOGY, 2024-01-24) Pastorino, Gil A.; Sheraj, Ilir; Oral, Goksu; Gulec Taskiran, Aliye Ezgi; Palmisano, Ralph; Schneider-Stock, ReginePartial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model. An EMT-specific quantitative polymerase chain reaction (qPCR) array was used to screen for deregulated genes, leading to the establishment of an in silico gene signature that was correlated with poor disease-free survival in CRC patients along with the CRC consensus molecular subtype CMS4. Among the significantly deregulated p-EMT genes, a triple-gene signature consisting of SERPINE1, SOX10, and epidermal growth factor receptor (EGFR) was identified. Starvation-induced p-EMT was characterised by increased migratory potential and chemoresistance, as well as E-cadherin processing and internalisation. Both gene signature and E-cadherin alterations could be reversed by the proteasomal inhibitor MG132. Spatially resolving EGFR expression with high-resolution immunofluorescence imaging identified a proliferation stop in starved CRC cells caused by EGFR internalisation. In conclusion, we have gained insight into a previously undiscovered EMT mechanism that may become relevant when tumour cells are under nutrient stress, as seen in early stages of metastasis. Targeting this process of tumour cell dissemination might help to prevent EMT and overcome drug resistance. (c) 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.Item Acute Stroke Management in Türkiye: Intravenous Tissue Plasminogen Activator and Thrombectomy NöroTek: Türkiye Neurology Single Day Study(2023) Arlier, Zulfikar; Can, UfukObjective: To reveal the profile and practice in patients with acute stroke who received intravenous tissue plasminogen activator (IV tPA) and/or neurointerventional therapy in Turkiye. Materials and Methods: On World Stroke Awareness Day, May 10, 2018, 1,790 patients hospitalized in 87 neurology units spread over 30 health regions were evaluated retrospectively and prospectively. Results: Intravenous tPA was administered to 12% of 859 cases of acute ischemic stroke in 45 units participating in the study. In the same period, 8.3% of the cases received neurointerventional treatment. The rate of good prognosis [modified Rankin score (mRS) 0-2] at discharge was 46% in 83 patients who received only IV tPA [age: 67 +/- 12 years; National Institutes of Health Stroke Scale (NIHSS): 12 +/- 6; hospital stay, 24 +/- 29 days]; 35% in 51 patients who underwent thrombectomy (MT) alone (age: 64 +/- 13 years; NIHSS: 14.1 +/- 6.5; length of hospital stay, 33 +/- 31 days), 19% in those who received combined treatment (age: 66 +/- 14 years; NIHSS: 15.6 +/- 5.4; length of hospital stay, 26 +/- 35 days), and 56% of 695 patients who did not receive treatment for revascularization (age: 70 +/- 13 years; NIHSS: 7.6 +/- 7.2; length of hospital stay, 21 +/- 28 days). The symptom-to-door time was 87 +/- 53 minutes in the IV treatment group and 200 +/- 26 minutes in the neurointerventional group. The average door-to-needle time was 66 +/- 49 minutes in the IV tPA group. In the neurothrombectomy group, the door-to-groin time was 103 +/- 90 minutes, and the TICI 2b-3 rate was 70.3%. In 103 patients who received IV tPA, the discharge mRS 0-2 was 41%, while the rate of mRS 0-1 was 28%. In 71 patients who underwent neurothrombectomy, the mRS 0-2 was 31% and mRS 0-1 was 18%. The door-to-groin time was approximately 30 minutes longer if IV tPA was received (125 +/- 107 and 95 +/- 83 minutes, respectively). Symptomatic bleeding rates were 4.8% in IV recipients, 17.6% among those who received only MT, and 15% in combined therapy. Globally, the hemorrhage rate was 6.8% in patients receiving IV tPA and 16.9% in MT. Conclusion: IV thrombolytic and neurointerventional treatment applications in acute ischemic stroke in Turkiye can provide the anticipated results. Heterogeneity has begun to be reduced in our country with the dissemination of the system indicated by the "Directive on Health Services to be Provided to Patients with Acute Stroke."Item The Prognostic Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) in Stage IIIC Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy(2023) Topkan, Erkan; Selek, Ugur; Pehlivan, Berrin; Kucuk, Ahmet; Ozturk, Duriye; Ozdemir, Beyza Sirin; Besen, Ali Ayberk; Mertsoylu, Huseyin; 0000-0001-8120-7123; 37760482; AAG-2213-2021Simple Summary: We investigated the prognostic significance of the newly created Global Immune-Nutrition-Inflammation Index (GINI) in IIIC non-small cell lung cancer (NSCLC) patients who received definitive concurrent chemoradiotherapy (CCRT). A total of 802 newly diagnosed stage IIIC NSCLC patients were included. The optimal pre-CCRT GINI cutoff was 1562 (area under the curve: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). GINI >= 1562 was associated with significantly shorter median locoregional progression-free (p < 0.001), progression-free (p < 0.001), and overall survival (p < 0.001) than GINI < 1562. For each survival endpoint, the association between GINI and survival outcomes appeared independent of other confounding variables (p < 0.05 for each). The novel GINI index effectively stratified patients with stage IIIC NSCLSC into two distinct subgroups, demonstrating significant differences in both median and long-term survival rates. Background: We sought to determine the prognostic value of the newly developed Global Immune-Nutrition-Inflammation Index (GINI) in patients with stage IIIC non-small cell lung cancer (NSCLC) who underwent definitive concurrent chemoradiotherapy (CCRT). Methods: This study was conducted on a cohort of 802 newly diagnosed stage IIIC NSCLC patients who underwent CCRT. The novel GINI created first here was defined as follows: GINI = [C-reactive protein x Platelets x Monocytes x Neutrophils] divided by [Albumin x Lymphocytes]. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal pre-CCRT GINI cut-off value that substantially interacts with the locoregional progression-free (LRPFS), progression-free (PFS), and overall survival (OS). Results: The optimal pre-CCRT GINI cutoff was 1562 (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). Patients presenting with a GINI >= 1562 had substantially shorter median LRPFS (13.3 vs. 18.4 months; p < 0.001), PFS (10.2 vs. 14.3 months; p < 0.001), and OS (19.1 vs. 37.8 months; p < 0.001) durations than those with a GINI < 1562. Results of the multivariate analysis revealed that the pre-CCRT GINI >= 1562 (vs. <1562), T4 tumor (vs. T3), and receiving only 1 cycle of concurrent chemotherapy (vs. 2-3 cycles) were the factors independently associated with poorer LRPS (p < 0.05 for each), PFS (p < 0.05 for each), and OS (p < 0.05 for each). Conclusion: The newly developed GINI index efficiently divided the stage IIIC NSCLSC patients into two subgroups with substantially different median and long-term survival outcomes.Item High Pretreatment Neutrophil-Lymphocyte Ratio: A Poor Prognostic Factor for Stage III Non-Small Cell Lung Cancer Patients(2015) Sumbul, Ahmet T.; Batmaci, Celal; Ucar, Edip; Kose, Fatih; Sedef, Ali M.; Yildirim, Berna; Mertsoylu, Huseyin; Sezer, Ahmet; Ozyilkan, Ozgur; 0000-0002-1932-9784; 0000-0001-8825-4918; 0000-0001-6661-4185; 0000-0002-5573-906X; M-9530-2014; AAD-2817-2021; V-5717-2017; D-4793-2014Item Prognostic Role of fox-p3 Positive T-Regulatory Cells in Curatively Resected NSCLC Other than Stage IA(2015) Kose, Fatih; Besen, Ayberk; Findikcioglu, Alper; Canbolat, Tuba; Ozdemir, Yurday; Sedef, Ali M.; Mertsoylu, Huseyin; Sumbul, Ahmet T.; Ozyilkan, Ozgur; Abali, Huseyin; 0000-0002-2218-2074; 0000-0002-1932-9784; 0000-0001-5596-0920; 0000-0002-7862-0192; 0000-0001-8825-4918; 0000-0002-5573-906X; AAG-5629-2021; M-9530-2014; D-7660-2016; AAD-6910-2021; AFT-2303-2022; AAD-2817-2021; D-4793-2014Item Clinical Use of Tumor Markers for the Detection and Prognosis of Bladder Carcinoma: A Comparison of CD44, Cytokeratin 20 and Survivin(2016) Yikilmaz, Taha Numan; Dirim, Ayhan; Ayva, Ebru Sebnem; Ozdemir, Handan; Ozkardes, Hakan; https://orcid.org/0000-0003-2898-485X; https://orcid.org/0000-0002-2280-8778; https://orcid.org/0000-0002-7528-3557; https://orcid.org/0000-0002-7277-449X; 27351322; AAJ-5689-2021; AAK-1967-2021; X-8540-2019; AAH-1052-2020Purpose: To investigate the role of CD44, cytokeratin 20 (CK20) and survivin for the detection and prognosis of patients with urothelial carcinoma of the bladder. Materials and Methods: The study included 82 patients who underwent transurethral resection of bladder tumors between 2009 and 2014. The patient and tumor characteristics with relevance to age, tumor size and focality, grade and stage, recurrence and progression were noted. Patients with carcinoma in situ, those who had at more than 3 sites of lesions and greater than 3 cm tumors were excluded. All cases were ex-smokers. All histological samples stained with hematoxylin and eosin were re-evaluated according to the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification system and immunohistochemically stained for CD44, CK20 and survivin. Results: The study group comprised 57 (69.5%) males and 25 (30.5%) females with a mean age of 60 years (range, 26-87 years). All were newly-diagnosed patients with bladder tumors. Immunohistochemical evaluation revealed that there was a statistically significant correlation between the grade and stage of the tumor with CK20 and survivin positivity (P < .05). As the grade and stage increased CD44 immunoreactivity significantly decreased (P = .002, P = .0001, respectively). However, relationship of protein expressions with recurrence and progression remained insignificant (P > .05). Conclusion: In cases of bladder urothelial carcinoma positivity for CD44, CK20, and survivin has significant relation with the tumor grade and stage while no significant relationship was determined in terms of recurrence and progressionItem Stromal Podoplanin Expression And Its Clinicopathological Role in Breast Carcinoma(2018) 30173230Introduction: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters. Materials & Methods: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with >= 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive. Results: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p=0.012), tumour grade (p=0.032) and cerbB2 score (p=0.032). Discussion: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.Item Adding Taxane to Platin-5-Fluorouracil Combination Does Not Improve Survival Rate in Patients >= 65 Years of Age with Advanced Gastric Cancer: A Retrospective-Multicenter Study(2018) Gunaldi, Meral; Kose, Fatih; Demirci, Nebi Serkan; Gunduz, Seyda; Ozdemir, Nuriye; Kocoglu, Hakan; Okuturlar, Yildiz; Sedef, Ali Murat; Erdem, Dilek; Goksu, Sema Sezgin; https://orcid.org/0000-0002-0156-5973; 29745086; G-4827-2016Purpose: Advanced gastric cancer (AGC) has a dismal prognosis. Platin-5-fluorouracil (CF) combination chemotherapy is the most widely used protocol and addition of a taxane (TCF) seems to increase survival and toxicity rates. We aimed to evaluate efficacy and toxicity of TCF as compared to CF in patients older than 65 years and compare them with the patients younger than 65 years. Methods: A total of 341 patients with AGC have been treated at six different oncology centers in Turkey between 2010 and 2014 and evaluated retrospectively. The characteristics of the patients whose tumors were histologically confirmed and whose survival data were available were registered and analyzed. The study group consisted of 234 patients younger than 65 years (group 1) and 107 patients older than 65 years (group 2). All of the data obtained from the patients were statistically analyzed. Results: The median age of the patients was 58.2 years and the mean follow-up time 14.4 months. For the entire group, progression-free survival (PFS) and overall survival OS) were 9 and 13 months, respectively. Using TCF over CF regimen increased the OS by 4.2 months (i.e., group 1 and 2 together). For group 2, patients with liver metastases and without surgery of the primary tumor were treated with significantly more TCF as compared to CF, respectively. Although TCF yielded significantly higher PFS and OS in group 1 (p=0.0001 and p=0.017), there was no significant difference in group 2 as compared to CF. Also, grade 3-4 toxicity was statistically defined as one of the possible reasons of worsened OS in patients older than 65 years and receiving TCF. Conclusions: The addition of taxanes to CF backbone leads to a significant increase in both PFS and OS in patients younger than 65 years of age but the triplet regimen with taxanes does not provide superior survival in patients older than 65 years of age.Item High Measures of Pre-Chemoradiotherapy Platelet-to-Albumin Ratio Indicates Poor Prognosis in Locally Advanced Pancreatic Cancer Patients(2022) Kucuk, Ahmet; Topkan, Erkan; Selek, Ugur; Haksoyler, Veysel; Mertsoylu, Huseyin; Besen, Ali Ayberk; Pehlivan, Berrin; https://orcid.org/0000-0001-8120-7123; 35444422; AAG-2213-2021Purpose: In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on the survival results of locally advanced unresectable pancreatic adenocarcinoma (LAPC) patients. Patients and Methods: The present analysis included 139 LAPC patients who received C-CRT in total. The utility of pre-C-CRT cutoff(s) reshaping survival data was explored using receiver operating characteristic (ROC) curve analysis. The primary and secondary objectives were the associations between PAR levels and overall survival (OS) and progression-free survival (PFS) outcomes. Results: At a median follow-up of 15.7 months (95% CI: 11.6-19.8), the overall cohort's median and 5-year OS rates were 14.4 months (95% CI: 11.8-17) and 14.7%, respectively, while the corresponding PFS rates were 7.8 months (95% CI: 6.5-9.1) and 11.2%. Because the ROC curve analysis found 4.9 as the optimal PAR cutoff for both OS and PFS [area under the curve (AUC): 75.4%; sensitivity: 72.4%; specificity: 70.3%], we divided the patients into two PAR cohorts: PAR<4.9 (N=60) and PAR>4.9 (N=79). Comparative analysis per PAR group exhibited significantly worse OS (11.2 vs 18.6 months, and 9.8% vs 20.9% at 5 years, P=0.003) and DFS (7 vs 14.3 months, and 7.6% vs 16.2% at 5 years, P=0.001) with PAR>4.9 versus PAR<4.9, respectively. In multivariate analysis, the N0 nodal status, CA 19-9 <= 90 U/mL, and PAR<4.9 were found to be independent predictors of improved OS and PFS. Conclusion: The pre-C-CRT high PAR (>4.9) robustly and independently prognosticated significantly worse OS and PFS results in inoperable LAPC patients who underwent definitive C-CRT.Item Does Lymph Node Ratio (Metastasis/Total Lymph Node Count) Affect Survival And Prognosis In Gastric Cancer?(2022) Topcu, Ramazan; Sahiner, Ibrahim T.; Kendirci, Murat; Erkent, Murathan; Sezikli, Ismail; Tutan, Mehmet B.; https://orcid.org/0000-0002-3592-5092; 35110338; GVS-3968-2022; CAA-2756-2022Objectives: To investigate the influence of the metastatic lymph node/total lymph node ratio (N- ratio) on survival and prognosis in surgically treated gastric carcinomas. Methods: A retrospective review of 73 patients who underwent curative resection at the Department of General Surgery, Hitit University Faculty of Medicine, Turkey. Receiver operating characteristic analysis was used to calculate the cut-off value for the N-ratio of the patients. The N-ratio cut-off value was determined to be 0.32. Patients were divided into 2 groups: below 0.32 (Group 1) and 0.32 and above 0.32 (Group 2). Results: Group 2 patients had a total lymph node mean of 25.10 +/- 13.64 while Group 1 patients had a total lymph node mean of 18.77 +/- 9.36 (p=0.04). In Group 2, the mean of metastatic lymph node was 15.97 +/- 10.30 (p<0.001). The mortality rate of Group 1 was 18% while Group 2 was 51.7%, and were statistically significant (p=0.0039). The estimated survival duration of Group 2 was 24.22 months, and Group 1 was 48.01 months (p=0.001). The mean estimated survival time for the entire group was 40.92 months. We differentiated patients from the development of mortality cut-off value in ROC analysis with 65.2% sensitivity and 72% specificity. This ratio was found to be 0.32, which was statistically significant (p=0.003). Ratios greater than 0.32 raised the risk of mortality by 4.8 times, which was statistically significant (p=0.003). Conclusion: The N-ratio could be a new metric to evaluate prognosis following curative gastrectomy and improve the existing tumor lymph node metastasis staging system.
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